This Program Project is a major endeavor aimed at understanding how proteins interact with DNA and facilitate tissue-specific and endocrinologic control of genes for proteins involved in intermediary metabolism. The program is organized around (1) support for largely collaborative research projects, (2) bringing together scientists from several departments (3) developing core resources in gene expression and transgenic mice (4) having an administrative core dedicated to providing cohesion and interaction within the program, (5) bringing in consultants for intensive interaction and finally (6) organizing a micro-sabbatical device to enable members of the team to take short (2-16 day) off campus assignments to learn new techniques and approaches. The members of the group are all interested in the control of gene activity through DNA/protein interactions. Project #1 (RC/BH) involves a study of the tissue-specific development of a competent chromatin structure in the PEPCK gene. Project #2 (DKG and MAM) involves a study of the differential selection of tissue-specific promoters for the same, glucokinase, gene. Project #3 (RS and PAW) is a detailed in vivo and in vitro study of the control of the rat insulin gene. Project #4 (PAW) involves an analysis of the structure and function of yeast TFIID which the PI has recently cloned. Project #5 (WA) involves x-ray crystallographic analysis of DNA-CRO interactions; as well as studies of the structure of RNA polymerase II. This Program Project is important to the success of these studies for several reasons. First, it will provide a critical mass of people, closely situated, and with a common purpose. Second, it will add additional resources that can be immediately applied to the stated aims. Third, it will provide the means for the continual development of the technological approaches that are absolutely essential for future progress in this area. Finally, it will allow us, through the seminar series and off-campus development program, to stay abreast of this extremely rapidly moving field.